HomeRadiologyVol. 311, No. 1 PreviousNext CommunicationsLetters to the EditorCaution on the CONTRRAST TrialSarah Eskreis-Winkler , Maxine S. Jochelson, Katja Pinker, Janice S. Sung, Christopher ComstockSarah Eskreis-Winkler , Maxine S. Jochelson, Katja Pinker, Janice S. Sung, Christopher ComstockAuthor AffiliationsDepartment of Radiology, Memorial Sloan-Kettering Cancer Center, New York, 300 E 66th St, New York, NY 10065email: [email protected]Sarah Eskreis-Winkler Maxine S. JochelsonKatja PinkerJanice S. SungChristopher ComstockPublished Online:Apr 9 2024https://doi.org/10.1148/radiol.233188MoreSectionsFull textPDF ToolsAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookXLinked In Reference1. Phillips J, Mehta TS, Portnow LH, Fishman MDC, Zhang Z, Pisano ED. Comparison of Contrast-enhanced Mammography with MRI Utilizing an Enriched Reader Study: A Breast Cancer Study (CONTRRAST Trial). Radiology 2023;309(2):e230530. Link, Google ScholarArticle HistoryPublished online: Apr 09 2024 FiguresReferencesRelatedDetailsRecommended Articles Recall and Outcome of Screen-detected Microcalcifications during 2 Decades of Mammography Screening in the Netherlands National Breast Screening ProgramRadiology2020Volume: 294Issue: 3pp. 528-537Digital Breast Tomosynthesis May Not Provide Optimal Surveillance of Breast Cancer SurvivorsRadiology2020Volume: 298Issue: 2pp. 317-318Data Do Not Support Semiannual Screening US after MRI, and Screening Mammography after MRI Has Limited BenefitRadiology2023Volume: 307Issue: 5Contrast-enhanced Mammography: Current Applications and Future DirectionsRadioGraphics2019Volume: 39Issue: 7pp. 1907-1920Supplemental Breast Cancer Screening in Women with Dense Breasts and Negative Mammography: A Systematic Review and Meta-AnalysisRadiology2023Volume: 306Issue: 3See More RSNA Education Exhibits 2022 New Trends in Breast Density - What Should We Know?Digital Posters2022Let's Talk about Next-Generation Breast Cancer Screening Programs: How Should We Do? What Should We Use?Digital Posters2020AI for Mammography: What Radiologists Need to KnowDigital Posters2022 RSNA Case Collection Ductal carcinoma in situRSNA Case Collection2020Ductal Carcinoma In SituRSNA Case Collection2022Primary breast amyloidosisRSNA Case Collection2020 Vol. 311, No. 1 Metrics Altmetric Score PDF download

Apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (DWI) may help diagnose endometrial cancer (EC). However, the association between ADC and the recurrence and survival of EC remains unknown. We performed a systematic review and meta-analysis to investigate whether pretreatment ADC on DWI could predict the prognosis of women with EC. PubMed, Embase, and Cochrane's Library were searched for relevant cohort studies comparing the clinical outcomes between women with EC having low versus high ADC on pretreatment DWI. Two authors independently conducted data collection, literature searching, and statistical analysis. Using a heterogeneity-incorporating random-effects model, we analyzed the results. In the meta-analysis, 1358 women with EC were included from eight cohort studies and followed for a median duration of 40 months. Pooled results showed that a low pretreatment ADC on DWI was associated with poor disease-free survival (DFS, hazard ratio [HR]: 3.29, 95% CI: 2.04 to 5.31, p < 0.001; I2 = 41%). Subgroup analysis according to study design, tumor stage, MRI Tesla strength, ADC cutoff, follow-up duration, and study quality score showed consistent results (p for subgroup analysis all > 0.05). The predictive value of low ADC for poor DFS in women with EC decreased in multivariate studies compared to univariate studies (HR: 2.59 versus 32.57, p = 0.002). Further studies showed that a low ADC was also associated with poor overall survival (HR: 3.36, 95% CI: 1.33 to 8.50, p = 0.01, I2 = 0). In conclusion, a low ADC on pretreatment DWI examination may predict disease recurrence and survival in women with EC.

Number of subjects with DOSI scans performed at each time-point.

List of Chemotherapy regimens used in this study.

Supplemental Table 1: Participating centers that enrolled patients; Supplemental Table 2: Serial FMISO PET Imaging.

Background Despite growing interest in using contrast-enhanced mammography (CEM) for breast cancer screening as an alternative to breast MRI, limited literature is available. Purpose To determine whether CEM is noninferior to breast MRI or abbreviated breast MRI (AB MRI) and superior to two-dimensional mammography in an asymptomatic population simulating those who would present for screening and then undergo diagnostic work-up. Materials and Methods This enriched reader study used CEM and MRI data prospectively collected from asymptomatic individuals at a single institution from December 2014 to March 2020. Case sets were obtained at screening, as part of work-up for a screening-detected finding, or before biopsy of a screening-detected abnormality. All images were anonymized and randomized, and all 12 radiologists interpreted them. For CEM interpretation, readers were first shown low-energy images as a surrogate for digital mammography and asked to give a forced Breast Imaging Reporting and Data System score for up to three abnormalities. The highest score was used as the case score. Readers then reviewed the full CEM examination and scored it similarly. After a minimum 1-month washout, the readers similarly interpreted AB MRI and full MRI examinations. Receiver operating characteristic analysis, powered to test CEM noninferiority to full MRI, was performed. Results The study included 132 case sets (14 negative, 74 benign, and 44 malignant; all female participants; mean age, 54 years ± 12 [SD]). The mean areas under the receiver operating characteristic curve (AUCs) for digital mammography, CEM, AB MRI, and full MRI were 0.79, 0.91, 0.89, and 0.91, respectively. CEM was superior to digital mammography (P < .001). No evidence of a difference in AUC was found between CEM and AB MRI and MRI. Conclusion In an asymptomatic study sample, CEM was noninferior to full MRI and AB MRI and was superior to digital mammography. Clinical trial registration no. NCT03482557 and NCT02275871 © RSNA, 2023 Supplemental material is available for this article.

Preterm birth is a leading cause of neonatal mortality in the US and globally, with preterm premature rupture of fetal membranes (PPROM) accounting for one third of preterm births. Currently no predictive diagnostics are available to precisely assess risk and potentially reduce the incidence of PPROM. Bigycan and decorin, the main proteoglycans present in human fetal membranes, are involved in the physiological maturation of fetal membranes as well as in the pathophysiology of preterm birth. The serum protein sex hormone-binding globulin (SHBG) has recently been identified as a predictor of spontaneous preterm birth. We hypothesize that the balance between serum decorin and biglycan on one hand and SHBG on the other hand may provide insight into the status of the fetal membranes in early pregnancy, thereby predicting PPROM prior to symptoms. Using chart review, 18 patients with confirmed cases of PPROM were identified from 2013-2016. Second trimester residual serum was retreived from freezer storage for these cases along with 5 matched controls for each case. The biomarkers biglycan, decorin and SHBG were analyzed first separately, then in combination to determine their ability to predict PPROM. The predictive score for the combined model displays an AUC = 0.774. The ROC curve of the predicted score has an optimal threshold of 0.238 and a sensitivity and specificity of 0.72 and 0.84 respectively. This prenatal serum panel is a promising serum screening-based biochemical model to predict PPROM in asymptomatic women.

Purpose: Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives. Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. Results: Of 107 women enrolled, 67 patients (median age 49, range 24-75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm(2)/s) than benign lesions [1.21 x 10(-3) vs. 1.47 x 10(-3); P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65-0.84]. In centralized analysis, application of an ADC threshold (1.53 x 10(-3) mm(2)/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%-31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 x 10(-3) mm(2)/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers. Conclusions: DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.

BackgroundACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS).MethodsTwo hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation). Four central readers measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing vs non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference.ResultsAdjusting for treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48-2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs 535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P = 0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01).ConclusionIncreased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by substratifying bevacizumab-treated patients with non-increasing 2D-T1.

Purpose: To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods: A total of 18 patients (mean age, 57 years +/- 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (K-trans) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (v(e)), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradientre-called acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. Results: Mean interreader variations (+/- standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median K-trans, and median v(e) were 18% +/- 24, 17% +/- 23, 27% +/- 34, 16% +/- 27, and 27% +/- 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. Conclusion: Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. (c) RSNA, 2018

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) “A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)”, was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment. Percentage change in tumor ADC from that before treatment (ΔADC) was measured at each time point. Performance for predicting pCR was assessed by using the area under the receiver operating characteristic curve (AUC) for the overall cohort and according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. Results The final analysis included 242 patients with evaluable serial imaging data, with a mean age of 48 years ± 10 (standard deviation); 99 patients had HR-positive (hereafter, HR+)/HER2-negative (hereafter, HER2-) disease, 77 patients had HR-/HER2- disease, 42 patients had HR+/HER2+ disease, and 24 patients had HR-/HER2+ disease. Eighty (33%) of 242 patients experienced pCR. Overall, ΔADC was moderately predictive of pCR at midtreatment/12 weeks (AUC = 0.60; 95% confidence interval [CI]: 0.52, 0.68; P = .017) and after treatment (AUC = 0.61; 95% CI: 0.52, 0.69; P = .013). Across the four disease subtypes, midtreatment ΔADC was predictive only for HR+/HER2- tumors (AUC = 0.76; 95% CI: 0.62, 0.89; P < .001). In a test subset, a model combining tumor subtype and midtreatment ΔADC improved predictive performance (AUC = 0.72; 95% CI: 0.61, 0.83) over ΔADC alone (AUC = 0.57; 95% CI: 0.44, 0.70; P = .032.). Conclusion After 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy. © RSNA, 2018 Online supplemental material is available for this article.

Background Quantitative diffusion‐weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker. Purpose To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi‐institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures. Study Type Prospective. Subjects In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer. Field Strength/Sequence DWI was acquired before and after patient repositioning using a four b‐value, single‐shot echo‐planar sequence at 1.5T or 3.0T. Assessment A QA procedure by trained operators assessed artifacts, fat suppression, and signal‐to‐noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast‐enhanced images. Twenty cases were evaluated multiple times to assess intra‐ and interoperator variability. Segmentation similarity was assessed via the Sørenson–Dice similarity coefficient. Statistical Tests Repeatability and reproducibility were evaluated using within‐subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients. Results In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane‐based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10 −3 mm 2 /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96). Data Conclusion Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi‐institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617–1628.

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3-to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO(2)) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC = 0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO(2) to surrounding tissue StO(2) are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

Abstract Purpose: ACRIN 6695 was a feasibility study investigating whether CT perfusion (CTP) biomarkers are associated with progression-free survival (PFS) at 6 months (PFS-6) in patients with advanced ovarian cancer who were treated with carboplatin and either dose-dense (weekly) or conventional (3-weekly) paclitaxel, with optional bevacizumab in the prospective phase III GOG-0262 trial. Experimental Design: ACRIN 6695 recruited participants with residual disease after primary cytoreductive surgery or planned interval cytoreduction following neoadjuvant therapy, to undergo CTP studies before (T0), 3 weeks (T1), and 4 weeks (T2) after chemotherapy initiation. Tumor blood flow (BF) and blood volume (BV) were derived with commercial software. Fisher exact tests assessed the associations of CTP biomarkers changes from T0 to T2 dichotomized at zero with PFS-6 and overall radiographic response rate, while Cox regression assessed the associations between CTP biomarker changes and PFS and overall survival (OS). Bonferroni correction was used to account for multiple comparisons. Results: Seventy-six of 120 enrolled patients from 19 centers were evaluable with a median age of 61 years. BV increase was significantly associated with lower chance of PFS-6 (P = 0.028), while BF achieves borderline significance (P = 0.053). In addition, BF increase was associated with shorter PFS (HR 2.9, 95% CI, 1.3–6.4, P = 0.008) and remained significant after adjusting for age, change in tumor volume, and surgery status (P = 0.007). Neither BF nor BV changes were significantly associated with treatment response rate or OS. Conclusions: Early CTP biomarkers measurement may provide early prognostic information for PFS in newly diagnosed ovarian cancer. Clin Cancer Res; 23(14); 3684–91. ©2017 AACR.

11520 Background: Diffusion-weighted (DW) MRI is a non-contrast technique that can reflect treatment-induced alterations in tumor microstructure and cellularity. ACRIN 6698 was performed as a sub-study of the I-SPY 2 TRIAL to evaluate quantitative DW MRI for early assessment of breast cancer response to neoadjuvant chemotherapy (NAC) in a multisite, multiplatform trial. Methods: The IRB-approved trial was performed at ten institutions. Of 406 enrolled breast cancer patients, 272 were randomized to treatment (12 weekly cycles paclitaxel+/-experimental agent, followed by AC) and underwent breast DW MRI at four time points: pre-NAC (T1), early-NAC after 3 cycles paclitaxel (T2), mid-NAC between paclitaxel and AC (T3) and post-NAC (T4). Tumor apparent diffusion coefficient (ADC) was measured at each time point and compared for patients with and without complete pathologic response (pCR) by Wilcoxon signed rank test. Exploratory analyses were performed across subtypes defined by hormone receptor (HR) and HER2 expression. Performance for predicting pCR was assessed by calculating the area under the ROC curve (AUC). Results: Of 272 treated patients, 227 comprised the final cohort (14 were excluded for missing MRI exams, 31 for poor image quality). Median patient age was 48 (range, 25-77) years, and 71/227 (31.3%) achieved pCR. Subtype groups were HR+/HER2+ (n = 38), HR+/HER2- (n = 95), HR-/HER2+ (n = 20), and HR-/HER2- (n = 74). For the full cohort (all subtypes and treatments), both ADC and change in ADC from T1 were significantly predictive of pCR at T3 (AUC = 0.63, 95% CI 0.55-0.71; AUC = 0.62, 95% CI 0.53-0.70, respectively), and also at T4. ADC measures were not predictive of pCR at either T1or T2. Stratifying by subtype showed change in ADC at T3 was more predictive in HR-/HER2+ (AUC = 0.86) and HR+/HER2- (AUC = 0.75) tumors than HR-/HER2- and HR+/HER2+ tumors (AUC = 0.59 and 0.56, respectively). Conclusions: DW MRI reflects cytotoxic effects of chemotherapy, and mid-treatment ADC was a predictive marker of pCR. The predictive value of ADC varied across biologic subtypes. Further work is needed to determine the comparative predictive value of ADC to other imaging metrics. Clinical trial information: NCT01564368.

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control.

Purpose To assess the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with diagnostic contrast material-enhanced computed tomography (CT) in detecting lymph node (LN) metastasis in high-risk endometrial cancer. Materials and Methods This prospective multicenter HIPAA-compliant study had institutional review board approval, and all participants gave written informed consent. Data were accrued between January 2010 and June 2013. Patients underwent PET/CT and pelvic and abdominal lymphadenectomy. Two hundred seven of 215 enrolled patients had PET/CT and pathologic examination results for the abdomen and pelvis. Mean patient age was 62.7 years ± 9.6 (standard deviation). Data in all 23 patients with a positive abdominal examination and in 26 randomly selected patients with a negative abdominal examination were used for this central reader study. Seven independent blinded readers reviewed diagnostic CT and PET/CT results in different sessions 1 month apart. Accuracy was calculated at the participant level, correlating abdominal (right and left para-aortic and common iliac) and pelvic (right and left external iliac and obturator) LN regions with pathologic results, respecting laterality. Reader-average sensitivities, specificities, and areas under the receiver operating characteristic curve (AUCs) of PET/CT and diagnostic CT were compared. Power calculation was for sensitivity and specificity in the abdomen. Results Sensitivities of PET/CT versus diagnostic CT for the detection of LN metastasis were 0.65 (95% confidence interval [CI]: 0.57, 0.72) versus 0.50 (95% CI: 0.43, 0.58) (P = .01) in the abdomen and 0.65 (95% CI: 0.57, 0.72) versus 0.48 (95% CI: 0.41, 0.56) (P = .004) in the pelvis. Corresponding specificities were 0.88 (95% CI: 0.83, 0.92) versus 0.93 (95% CI: 0.89, 0.96) (P = .11) and 0.93 (95% CI: 0.86, 0.96) versus 0.89 (95% CI: 0.82, 0.94) (P = .27), and AUCs were 0.78 (95% CI: 0.66, 0.89) versus 0.74 (95% CI: 0.63, 0.86) (P = .39) and 0.82 (95% CI: 0.71, 0.92) versus 0.73 (95% CI: 0.63, 0.84) (P = .02). Conclusion FDG PET/CT has satisfactory diagnostic accuracy in the detection of abdominal LN metastasis in high-risk endometrial cancer. Compared with diagnostic CT alone, addition of PET to diagnostic CT significantly increased sensitivity in both the abdomen and pelvis while maintaining high specificity. © RSNA, 2017 Online supplemental material is available for this article.

Introduction: In patients with atrial fibrillation (AF) both “rate control” and “rhythm control” therapies have distinct set of limitations. We sought to investigate the rates and reasons of crossover from an initially assigned rate control arm to rhythm control and from rhythm to rate control therapy in patients who were enrolled in the AFFIRM trial. Methods: We compared the characteristics of patients who continued in the initially assigned treatment arm versus those who crossed over to the alternative treatment strategy in both “rhythm” and “rate” control arms. Two-sample t-test and chi-squared tests were used to compare means and proportions respectively. Results: A total of 4,060 patients were enrolled in the AFFIRM trial and over a mean follow-up duration of 3.5 years, 842 of them underwent crossover from an initially assigned treatment arm. The rate of crossover from an initially assigned rhythm control arm (594/2033, 29.2%) was more frequent than the rate of crossover from rate control to rhythm control (248/2027, 12.2%, p < 0.0001). In the rhythm control arm, the patients who crossed over to rate control had a significantly higher incidence of prior failure of an antiarrhythmic drug (139/594, 23.4%) than in those who continued as assigned (210/1439, 14.6%, p < 0.0001). In the rate control arm, patients who crossed over to rhythm control were relatively younger (68.3 ± 8.2 vs. 69.7 ± 8.0 years in those who continued, p = 0.01). The leading reasons for crossover to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover to rhythm control were failure to control AF symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). The difference in crossover pattern was statistically significant (p < 0.0001). Conclusions: Rhythm control was abandoned more commonly than rate control in patients who were enrolled in the AFFIRM trial. Failure of antiarrhythmic drug therapy prior to randomization was a significant factor for crossover from rhythm to rate control. Patients who crossed over from rate to rhythm control were younger than those who continued. The crossover from rhythm to rate control was driven by the occurrence of adverse effects.